REVIEW DAVID H. NEUSTADT, MD* Clinical Professor of Medicine, University of Louisville School of Medicine, Louisville, KY Intra-articular injections for osteoarthritis of the knee ■ ABSTRACT NJECTION OF CORTICOSTEROIDS into I painful joints—long a mainstay of thera- If usual medical measures fail to control the pain of knee py for rheumatoid arthritis—is now popular osteoarthritis and allow the patient to cope with its for osteoarthritis of the knee as well. symptoms, intra-articular injections of a corticosteroid, a Logically, this use may seem surprising, hyaluronan, or both can be tried. since we used to be taught that osteoarthritis is due to “wear and tear,” not inflammation, and ■ KEY POINTS corticosteroids are powerful anti-inflammatory drugs. However, now we know that inflamma- Osteoarthritis is now known to involve more than tion is present in most patients with sympto- mechanical wear and tear, as believed in the past; matic osteoarthritis. Moreover, this treatment inflammatory mechanisms are also at work. often provides striking and lasting relief of pain, especially in patients with synovitis asso- Patient education should emphasize losing weight (in ciated with chronic knee osteoarthritis. overweight patients) and modifying activities to reduce A local (as opposed to a systemic) treat- stress on the knees, as well as what to expect from intra- ment for a painful joint has obvious appeal. articular therapy. Nevertheless, intra-articular corticosteroid ther- apy is essentially palliative and must be consid- ered as adjunctive to other basic therapies.1 A large, tense, or painful effusion is the strongest Newer agents called hyaluronans are also indication for prompt arthrocentesis and, if the synovial given by intra-articular injection. In the syno- fluid is not infected, subsequent corticosteroid injection. vial fluid they supplement endogenous hyaluronan, which serves as a lubricant and After a corticosteroid injection in the knee, the patient shock absorber. should remain in bed or at rest and avoid walking as This article reviews the rationale for and much as possible for 3 days, and then use crutches or a the practical aspects of intra-articular therapy cane for the next 2 to 3 weeks. with corticosteroids and hyaluronan prepara- tions in osteoarthritis. The major factors that influence the therapeutic response ■ to intra-articular injections of hyaluronan are the severity OSTEOARTHRITIS IS COMMON of the disease and the extent of cartilage loss in the Osteoarthritis (also called degenerative joint involved knee. disease and osteoarthrosis) is by far the most common form of arthritis and the major cause of disability and reduced activity in people older than 50 years.2 The joint most often affected is the knee. *The author has indicated that he has served as a consultant for the Ortho Biotech Products According to some population surveys, 30% of corporation. people older than 50 years have radiographic CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 73 • NUMBER 10 OCTOBER 2006 897 Downloaded from www.ccjm.org on October 3, 2021. For personal use only. All other uses require permission. OSTEOARTHRITIS NEUSTADT evidence of osteoarthritis of the knee, increas- relative comfort. Therapy is individualized on ing to up to 80% after age 65. In the United the basis of the symptoms and severity of the States, approximately 100,000 people are disease; options range from simple advice unable to walk independently from bed to about modifying activity to joint replacement. bathroom owing to pain and disability caused by osteoarthritis of the knees. About 300,000 Nonpharmacologic measures are important knee joints were surgically replaced in 2005.3 Some of the most important nonpharmacologic Men have more knee osteoarthritis before measures aim at “deloading” the knee. Patients age 50, but its incidence in women rises after should try to lose weight if needed and protect menopause, and by age 65 the prevalence is the knees by avoiding up-and-down impact on twice as high in women as in men.4 them, using walking aids such as canes and crutches. They should also avoid climbing stairs ■ NOT JUST WEAR AND TEAR and should regularly do isometric exercise to strengthen the quadriceps muscles. Osteoarthritis is characterized by cartilage Some patients with osteoarthritis of the involvement, varying from microfissures and medial compartment of the knee get some fibrillations in early disease to virtual destruc- relief by placing wedges in their shoes in the tion with bone-on-bone contact in advanced lateral heel and insole.5 In a study of 85 disease. Osteophytes (spurs) develop at the patients (with 121 osteoarthritic knees) treat- margins of joints, and new cartilage prolifer- ed for approximately 1 year, 61% reported a ates over these bony spurs. favorable response to this simple measure.5,6 During the past decade much has been Of paramount importance is patient edu- learned about cartilage, including metabolic cation. It should emphasize what to expect changes, genetic mutations, metallopro- and the importance of losing weight, especial- teinases, and inflammatory mediators, foster- ly in vastly overweight patients, and of modi- ing considerable excitement and interest in fying their activities. new approaches for preventing and treating Options range osteoarthritis. Simple analgesics, NSAIDs for minimal pain from simple Although the specific cause of osteoarthri- If pain is minimal, it may be controlled with tis remains unknown, contributing and risk simple analgesics such as acetaminophen advice to joint factors include: (Tylenol), propoxyphene (Darvon), or tra- replacement • Aging madol (Ultram). Undesirable effects of these • Genetic factors medications are usually minor, but patients • Overweight and obesity with preexisting renal or liver conditions must • Overuse of the joints (as in occupational exercise special caution. and sports activities) If simple analgesics do not adequately •Trauma control the pain, one can add a nonsteroidal •Malalignment of the knee anti-inflammatory drug (NSAID). The many •Muscle weakness. traditional (nonselective) NSAIDs all have Osteoarthritis may be considered a “final similar efficacy, but they differ in gastrointesti- common pathway” resulting from a host of nal toxicity and in the number of tablets or these different problems, or it may be consid- capsules that need to be taken to reach the ered as primary or idiopathic when none of appropriate dose. The newer cyclooxygenase- these risk factors can be identified. 2-specific NSAIDs are as effective as the older, nonselective NSAIDs and have fewer gas- ■ MANAGEMENT IS INDIVIDUALIZED trointestinal side effects, but they are much more costly and some appear to increase the No specific therapy has yet been clearly shown risk of cardiovascular events. to prevent the progression of osteoarthritis. The goal is to suppress pain and improve func- Intra-articular injections tion, with special attention to the patent’s Concerned about possible side effects of selec- ability to rise from a low seat and walk with tive and nonselective NSAIDs, physicians are 898 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 73 • NUMBER 10 OCTOBER 2006 Downloaded from www.ccjm.org on October 3, 2021. For personal use only. All other uses require permission. increasingly considering intra-articular treat- Most authorities now consider intra-artic- ment when simple measures are inadequate. ular corticosteroid therapy for osteoarthritis of Some intra-articular treatments have not considerable value when used appropriately been beneficial. In a randomized study in 180 and judiciously.18 patients with osteoarthritis of the knee, joint lavage with saline was no more beneficial than Metabolism of corticosteroid suspensions: a sham procedure.7 Arthroscopy with or with- Systemic absorption may occur out debridement is also ineffective in osteo- The metabolic pathway and ultimate fate of arthritis of the knee unless secondary damage corticosteroids within the joint have not been such as troublesome loose bodies or a torn completely elucidated.10 Injected steroids can meniscus is present, requiring surgical repair.8 be detected in synovial fluid cells for 48 hours On the other hand, intra-articular corti- after injection.19 The rate of absorption and the costeroid therapy is often successful in knee duration of action are related to the solubility of osteoarthritis associated with synovitis and the compound injected. Triamcinolone hexace- effusion. Steroid injections may be given up to tonide (Aristospan) is the most insoluble prepa- three or four times per year. Injections of ration currently available.20 hyaluronans also seem to work. These thera- Systemic absorption may occur, varying pies are the focus of the rest of this article. with the dose and the solubility of the prepa- ration. One study showed that 40 mg of intra- Knee replacement articular methylprednisolone acetate (Depo- when medical therapy fails Medrol) was sufficient to transiently suppress Knee replacement is reserved for patients for adrenal function, as reflected in depressed cor- whom medical management (including injec- tisol levels for up to 7 days.19 We ask patients tion therapy) fails, and for those who have to limit their activity after injections, as it intractable pain and disability. may delay escape of the steroid and minimize systemic effects (see below). ■ INTRA-ARTICULAR CORTICOSTEROIDS Therapeutic rationale for corticosteroids Important Hydrocortisone was introduced for intra-artic- Corticosteroids